RU2008112205A - SULFONAMIDE COMPOUND - Google Patents

SULFONAMIDE COMPOUND Download PDF

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RU2008112205A
RU2008112205A RU2008112205/04A RU2008112205A RU2008112205A RU 2008112205 A RU2008112205 A RU 2008112205A RU 2008112205/04 A RU2008112205/04 A RU 2008112205/04A RU 2008112205 A RU2008112205 A RU 2008112205A RU 2008112205 A RU2008112205 A RU 2008112205A
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Ринтаро ЯМАДА (JP)
Ринтаро ЯМАДА
Минору СЭТО (JP)
Минору СЭТО
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Асахи Касеи Фарма Корпорэйшн (Jp)
Асахи Касеи Фарма Корпорэйшн
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Abstract

1. Соединение, представленное нижеследующей общей формулой (1), или его соль, или его производное, которое представляет собой пролекарство: ! ! в формуле A представляет собой азотсодержащее насыщенное кольцо; ! m представляет собой целое число, равное 0, 1 или 2; ! n представляет собой целое число, равное 1, 2, 3 или 4; ! G1 представляет собой атом водорода, атом хлора, гидроксильную группу, алкоксигруппу или аминогруппу; ! G2 представляет собой атом галогена, гидроксильную группу, цианогруппу, карбоксигруппу, алкильную группу, которая может быть замещенной, алкенильную группу, которая может быть замещенной, алкинильную группу, которая может быть замещенной, алкоксигруппу, которая может быть замещенной, алкилтиогруппу, которая может быть замещенной, аминогруппу, которая может быть замещенной, алкилсульфинильную группу, которая может быть замещенной, алкилсульфонильную группу, которая может быть замещенной, или арильную группу, которая может быть замещенной; ! G3 представляет собой атом водорода, атом галогена, гидроксильную группу, цианогруппу, карбоксигруппу, алкильную группу, которая может быть замещенной, алкенильную группу, которая может быть замещенной, алкинильную группу, которая может быть замещенной, алкоксигруппу, которая может быть замещенной, алкилтиогруппу, которая может быть замещенной, аминогруппу, которая может быть замещенной, алкоксикарбонильную группу, которая может быть замещенной, ацильную группу, которая может быть замещенной, ацилоксигруппу, которая может быть замещенной, алкилсульфинильную группу, которая может быть замещенной, алкилсульфонильную группу, которая может быть замещенной, или арильну�1. The compound represented by the following general formula (1), or a salt thereof, or a derivative thereof, which is a prodrug:! ! in the formula, A represents a nitrogen-containing saturated ring; ! m is an integer equal to 0, 1 or 2; ! n is an integer equal to 1, 2, 3 or 4; ! G1 represents a hydrogen atom, a chlorine atom, a hydroxyl group, an alkoxy group or an amino group; ! G2 represents a halogen atom, a hydroxyl group, a cyano group, a carboxy group, an alkyl group which may be substituted, an alkenyl group which may be substituted, an alkynyl group which may be substituted, an alkoxy group which may be substituted, an alkylthio group which may be substituted an amino group which may be substituted, an alkylsulfinyl group which may be substituted, an alkylsulfonyl group which may be substituted, or an aryl group which may be substituted ; ! G3 represents a hydrogen atom, a halogen atom, a hydroxyl group, a cyano group, a carboxy group, an alkyl group which may be substituted, an alkenyl group which may be substituted, an alkynyl group which may be substituted, an alkoxy group which may be substituted, an alkylthio group which may be substituted, an amino group which may be substituted, an alkoxycarbonyl group which may be substituted, an acyl group which may be substituted, an acyloxy group which may be substituted th, an alkylsulfinyl group which may be substituted, an alkylsulfonyl group which may be substituted, or an aryl

Claims (22)

1. Соединение, представленное нижеследующей общей формулой (1), или его соль, или его производное, которое представляет собой пролекарство:1. The compound represented by the following general formula (1), or a salt or derivative thereof, which is a prodrug:
Figure 00000001
Figure 00000001
 в формуле A представляет собой азотсодержащее насыщенное кольцо;in the formula, A represents a nitrogen-containing saturated ring; m представляет собой целое число, равное 0, 1 или 2;m is an integer equal to 0, 1 or 2; n представляет собой целое число, равное 1, 2, 3 или 4;n is an integer equal to 1, 2, 3 or 4; G1 представляет собой атом водорода, атом хлора, гидроксильную группу, алкоксигруппу или аминогруппу;G 1 represents a hydrogen atom, a chlorine atom, a hydroxyl group, an alkoxy group or an amino group; G2 представляет собой атом галогена, гидроксильную группу, цианогруппу, карбоксигруппу, алкильную группу, которая может быть замещенной, алкенильную группу, которая может быть замещенной, алкинильную группу, которая может быть замещенной, алкоксигруппу, которая может быть замещенной, алкилтиогруппу, которая может быть замещенной, аминогруппу, которая может быть замещенной, алкилсульфинильную группу, которая может быть замещенной, алкилсульфонильную группу, которая может быть замещенной, или арильную группу, которая может быть замещенной;G 2 represents a halogen atom, a hydroxyl group, a cyano group, a carboxy group, an alkyl group which may be substituted, an alkenyl group which may be substituted, an alkynyl group which may be substituted, an alkoxy group which may be substituted, an alkylthio group which may be substituted, an amino group which may be substituted, an alkylsulfinyl group which may be substituted, an alkylsulfonyl group which may be substituted, or an aryl group which may be substituted th; G3 представляет собой атом водорода, атом галогена, гидроксильную группу, цианогруппу, карбоксигруппу, алкильную группу, которая может быть замещенной, алкенильную группу, которая может быть замещенной, алкинильную группу, которая может быть замещенной, алкоксигруппу, которая может быть замещенной, алкилтиогруппу, которая может быть замещенной, аминогруппу, которая может быть замещенной, алкоксикарбонильную группу, которая может быть замещенной, ацильную группу, которая может быть замещенной, ацилоксигруппу, которая может быть замещенной, алкилсульфинильную группу, которая может быть замещенной, алкилсульфонильную группу, которая может быть замещенной, или арильную группу, которая может быть замещенной (при условии, что заместители G3 находятся в 3-, 6-, 7- или 8-положении изохинолинового кольца);G 3 represents a hydrogen atom, a halogen atom, a hydroxyl group, a cyano group, a carboxy group, an alkyl group which may be substituted, an alkenyl group which may be substituted, an alkynyl group which may be substituted, an alkoxy group which may be substituted, an alkylthio group, which may be substituted, an amino group which may be substituted, an alkoxycarbonyl group which may be substituted, an acyl group which may be substituted, an acyloxy group which may be substituted minutes, an alkylsulfinyl group which may be substituted, an alkylsulfonyl group which may be substituted, or an aryl group which may be substituted (provided that G 3 are substituents at the 3-, 6-, 7- or 8-position of the isoquinoline ring ); G4 представляет собой гидроксильную группу или -N(R1)(R2) (R1 и R2 могут быть одинаковыми или различными, и независимо представляют собой атом водорода, алкильную группу, которая может быть замещенной, аралкильную группу, которая может быть замещенной, алкенильную группу, которая может быть замещенной, алкинильную группу, которая может быть замещенной, или насыщенную гетероциклическую группу, которая может быть замещенной); иG 4 represents a hydroxyl group or —N (R 1 ) (R 2 ) (R 1 and R 2 may be the same or different, and independently represent a hydrogen atom, an alkyl group that may be substituted, an aralkyl group that may be a substituted, alkenyl group which may be substituted, an alkynyl group which may be substituted, or a saturated heterocyclic group which may be substituted); and G5 представляет собой заместитель при углеродном атоме, составляющем азотсодержащее насыщенное кольцо, представленное А, и представляет собой атом водорода, атом фтора или алкильную группу.G 5 represents a substituent at the carbon atom constituting the nitrogen-containing saturated ring represented by A, and represents a hydrogen atom, a fluorine atom or an alkyl group. 2. Соединение, или его соль, или производное, которое представляет собой пролекарство, по п.1, где m равно 1.2. The compound, or its salt, or derivative, which is a prodrug, according to claim 1, where m is 1. 3. Соединение, или его соль, или производное, которое представляет собой пролекарство, по п.1 или 2, где n равно 2 или 3.3. The compound, or its salt, or derivative, which is a prodrug, according to claim 1 or 2, where n is 2 or 3. 4. Соединение, или его соль, или производное, которое представляет собой пролекарство, по п.1, где G3 представляет собой атом водорода.4. The compound, or its salt, or derivative, which is a prodrug, according to claim 1, where G 3 represents a hydrogen atom. 5. Соединение, или его соль, или производное, которое представляет собой пролекарство, по п.1, где G5 представляет собой атом водорода.5. The compound, or its salt, or derivative, which is a prodrug, according to claim 1, where G 5 represents a hydrogen atom. 6. Соединение, или его соль, или производное, которое представляет собой пролекарство, по п.1, где G4 представляет собой -N(R1)(R2).6. The compound, or its salt, or derivative, which is a prodrug, according to claim 1, where G 4 represents —N (R 1 ) (R 2 ). 7. Лекарственное средство, содержащее соединение, его соль или его производное, которое представляет собой пролекарство, по любому из пп.1-6 в качестве активного ингредиента.7. A medicament containing a compound, a salt thereof or a derivative thereof, which is a prodrug, according to any one of claims 1 to 6, as an active ingredient. 8. Лекарственное средство по п.7, которое ингибирует фосфорилирование регуляторной легкой цепи миозина.8. The drug according to claim 7, which inhibits the phosphorylation of the regulatory light chain of myosin. 9. Лекарственное средство по п.7, которое ингибирует путь киназы Rho/Rho.9. The drug according to claim 7, which inhibits the Rho / Rho kinase pathway. 10. Лекарственное средство по п.7, которое используют для профилактики и/или лечения глаукомы.10. The drug according to claim 7, which is used for the prevention and / or treatment of glaucoma. 11. Ингибитор фосфорилирования регуляторной легкой цепи миозина, содержащий соединение, его соль или его производное, которое представляет собой пролекарство, по любому из пп.1-6.11. The phosphorylation inhibitor of the regulatory myosin light chain containing the compound, its salt or its derivative, which is a prodrug, according to any one of claims 1 to 6. 12. Ингибитор пути киназы Rho/Rho, содержащий соединение, его соль или его производное, которое представляет собой пролекарство, по любому из пп.1-6.12. An Rho / Rho kinase pathway inhibitor comprising a compound, a salt thereof or a derivative thereof, which is a prodrug, according to any one of claims 1 to 6. 13. Лекарственное средство, содержащее соединение, его соль или его производное, которое представляет собой пролекарство, по п.1 и лекарственное средство, обладающее действием, снижающим внутриглазное давление, и/или лекарственное средство, обладающее защищающим оптический нерв действием, в комбинации.13. The drug containing the compound, its salt or its derivative, which is a prodrug, according to claim 1 and a drug having an action that reduces intraocular pressure, and / or a drug having an action protecting an optical nerve, in combination. 14. Лекарственное средство, содержащее соединение, его соль или его производное, которое является пролекарством, по п.1 и любое одно или несколько средств, выбранных из стимулятора адренергических рецепторов, простагландин-родственного средства, ингибитора углеродной ангидразы, блокатора адренергических рецепторов, ингибитора холинэстеразы, антагониста кальция, ингибитора киназы Rho, антагониста рецепторов ангиотензина II и блокатора рецепторов NMDA, в комбинации.14. A drug containing a compound, its salt or its derivative, which is a prodrug, according to claim 1 and any one or more drugs selected from a stimulator of adrenergic receptors, a prostaglandin-related agent, a carbon anhydrase inhibitor, an adrenergic receptor blocker, a cholinesterase inhibitor Calcium antagonist, Rho kinase inhibitor, angiotensin II receptor antagonist and NMDA receptor blocker, in combination. 15. Лекарственное средство, содержащее в комбинации соединение, его соль или его производное, которое является пролекарством, по п.1 и лекарственное средство, обладающее действием, понижающим внутриглазное давление.15. A drug containing in combination a compound, its salt or its derivative, which is a prodrug, according to claim 1 and a drug having an action that reduces intraocular pressure. 16. Лекарственное средство, содержащее соединение, его соль или его производное, которое является пролекарством, по п.1 и любое одно или несколько средств, выбранных из простагландин-родственного средства, ингибитора углеродной ангидразы и блокатора адренергических рецепторов.16. A drug containing a compound, a salt thereof or a derivative thereof, which is a prodrug of claim 1, and any one or more agents selected from a prostaglandin-related agent, a carbon anhydrase inhibitor, and an adrenergic receptor blocker. 17. Лекарственное средство по п.16, которое представляет собой средство для профилактики и/или лечения глаукомы.17. The drug according to clause 16, which is an agent for the prevention and / or treatment of glaucoma. 18. Лекарственное средство, содержащее соединение, его соль или его производное, которое является пролекарством, по п.1 и лекарственное средство, обладающее защищающим оптический нерв действием, в комбинации.18. A drug containing a compound, a salt thereof or a derivative thereof, which is a prodrug of claim 1, and a drug having an optical nerve-protecting action in combination. 19. Лекарственное средство по п.16, где простагландин-родственное средство, указанное в п.16, представляет собой любое средство, выбранное из латанопроста, биматопроста, травопроста, изопропилунопростона и тафлупроста.19. The drug according to clause 16, where the prostaglandin-related product specified in clause 16, is any tool selected from latanoprost, bimatoprost, travoprost, isopropylunoproston and tafluprost. 20. Лекарственное средство по п.16, где ингибитор углеродной ангидразы, указанный в п.16, представляет собой любой один ингибитор, выбранный из гидрохлорида дорзоламида, гидрохлорида бринзоламида и гидрохлорида ацетазоламида.20. The drug according to clause 16, where the carbon anhydrase inhibitor specified in clause 16, is any one inhibitor selected from dorzolamide hydrochloride, brinzolamide hydrochloride and acetazolamide hydrochloride. 21. Лекарственное средство по п.16, где блокатор адренергических рецепторов, указанный в п.16, представляет собой любой один блокатор, выбранный из гидрохлорида буназосина, малеата тимолола, гидрохлорида картеолола, гидрохлорида левобунолола, гидрохлорида бетаксолола, гидрохлорида нипрадилола и гидрохлорида бефунолола.21. The drug according to clause 16, where the adrenergic receptor blocker specified in clause 16, is any one blocker selected from bunazosin hydrochloride, timolol maleate, cartolol hydrochloride, levobunolol hydrochloride, betaxolol hydrochloride, nipradilol hydrochloride and befunolol hydrochloride. 22. Способ терапевтического и/или профилактического лечения глаукомы, в котором используют лекарственное средство по любому из пп.13-21. 22. A method for the therapeutic and / or prophylactic treatment of glaucoma, which uses the drug according to any one of claims 13-21.
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